1. Field of the Invention
This invention relates to an elastomeric stopper used in conjunction with bottles and vials containing pharmaceutical products for parenteral administration. More particularly, the invention relates to an elastomeric stopper for hermetically sealing a parenteral bottle or vial which is accessed by the use of an infusion spike.
2. Reported Developments
Stopper systems for vials, bottles and the like are made of materials that are resistant to chemicals and pharmaceuticals such as corrosive materials, reagents, parenteral solutions and solid formulations reconstitutable with a solvent prior to use. The most commonly used stopper system for such products has been glass or plastic bottles and vials equipped with rubber stoppers made of elastomeric materials. The system appears to provide for good hermetical seal, safe storage and easy access to the content through the elastomeric stopper via the use of an infusion spike when withdrawal of the content is desired. The elastomeric stopper used generally comprises an elastomeric base, such as natural or synthetic rubber and an inert coating covering at least some portions of the stopper. The coating used includes chlorobutyl rubber, polymeric fluorocarbon resins such as polytetrafluoroethylene and various thermoplastic films. The coating is intended to insulate the elastomeric stopper base from the content of the container in order to prevent contact and possible chemical reactions therebetween.
The prior art has provided various constructions and configurations to meet the requirements of stopper systems for use in the chemical/pharmaceutical industry. See, for example U.S. Pat. Nos. 2,665,024; 2,848,130; 3,088,615; 3,313,439; 3,974,930; 4,133,441; 4,227,617 and 4,441,621.
One of the major concerns in all products, and especially pharmaceutical parenteral products, is the generation of particulate foreign matter which may contaminate such products. In order to eliminate macroscopic and microscopic particulates, elaborate measures have been taken to remove them, such as filtration of the product and special washing and drying of the stopper system components. These steps help assure that the products meet the requirements and guidelines of the pharmaceutical industry, such as compendia guidelines, when the products reach the point of use. However, at the point of use, such as in the case of a parenteral product, new particulate matter is frequently generated by the practitioner when the stopper is penetrated by an infusion spike. During such penetration a combination of elastic and plastic deformation of the stopper target are increases the stopper contact surface with the infusion spike as it is pressed into the stopper. Typically, untreated elastomeric stoppers offer a high degree of resistance against the exterior surface of the spike as the spike is being pushed into the penetration area. Most frequently, when stopper fragments are generated, they are the result of the elastomeric portion of the stopper being abraded off the upper surface of the stopper as it conforms to the shape of the penetrating spike. The fragments are then transported into the interior of the vial as the spike rolls and drags the fragments during penetration.
In addition to the problem of particulate matter produced and carried into the vial during the spiking procedure, there are two other problems: spike blow-out caused by residual elastic tension of the stopper against the spike which urges the spike outward; and leakage around the spike with or without the occurrence of blow-out.
During spike penetration of the elastomeric stopper the target membrane at the penetration site is elastically distorted and ruptured creating a seal that is not radially uniform between the spike and the ruptured membrane. This radial non-uniformity is an inherent characteristic of the target membrane area, which is first stretched and then is torn by the spike. The tear so produced develops axially rather than radially and the tear surface is jagged, uneven and does not provide for a good seal between the spike and the membrane. As a result, spike retention failure and leakage around the spike occurs. Such failures are especially significant when the container is pressurized.
The most common solution to these problems has been the application of silicone lubricant to the stopper and/or the spike to reduce the frictional drag between the stopper and the spike. While silicone does reduce particle generation from the spiking procedure, it also increases the risk of product contamination from its own composition. In addition, silicone lubrication of the stopper renders the inserted spike slippery and causes spike blow-out.
Another approach proposed in the prior art to reduce the tendency of the spike to generate particulate matter during penetration is to coat the elastomeric core of the stopper with a thermoplastic film on the fluid contacting side thereof. We have found, however, that the use of such construction is less than satisfactory to solve the problem. Furthermore, such construction does not provide for improved spike retention and reduced leakage tendency around the spike.
It is an object of the present invention to reduce the potential for leaking, reduce or eliminate the level of fragmentation and increase the spike insertion and especially the spike withdrawal force.
Accordingly, the present invention provides in a stopper a second seal upon insertion of the infusion spike into the stopper. This second seal is a dynamic seal created between an annular rim or protuberance of the stopper and the cylindrical shaft of the spike as the spike is being inserted into the stopper. The annular rim of the stopper is distorted with a slight elastic bend toward the center of the bottle creating a radially uniform seal between it and the spike. The frictional drag between the spike and the rim coupled with the natural tendency of the elastomer to return to is original position enhances the ability of the stopper to retain the infusion spike and produce a second seal in the stopper. In the event that the bottle should be pressurized, an additional force would be imparted on the second seal thereby enhancing the contact of the stopper with the infusion spike.